diabetes

Health Care Guideline

Diagnosis and Management of Type 2 Diabetes Mellitus in Adults

How to cite this document:

Redmon B, Caccamo D, Flavin P, Michels R, Myers C, OConnor P, Roberts J, Setterlund L, Smith S, Sperl-Hillen J. Institute for Clinical Systems Improvement. Diagnosis and Management of Type 2 Diabetes Mellitus in Adults. Updated July 2014.

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Health Care Guideline:

Diagnosis and Management of Type 2 Diabetes Mellitus in Adults

www.icsi.org Copyright 2014 by Institute for Clinical Systems Improvement 1

Sixteenth EditionJuly 2014

Text in blue in this algorithm indicates a linked corresponding annotation.

Diagnosis Algorithm

Assessment and diagnosis of T2DM

1

Asymptomatic patient Symptomatic patient

Does the patient have a BMI 25 kg/m2 and one or more

additional risk factors(see table)?

1.1

Does the patient have increased cardiovascular

risk (see table)?

1.2

no

Asymptomatic patients with no risk factors should not be screened for T2DM,

regardless of age

1.3

noDiagnostic testing for

T2DM A1c, OGTT or FPG

1.4

yes

Diagnosis of prediabetes A1c between 5.7-6.4% FPG between 100-125 mg/dL OGTT between 140-199 mg/dL

2

Go to the Management algorithm

Treatment to prevent or delay the progression to

T2DM

2.1

Risk Factors Table1.1 BMI 25 kg/m2 and one or more of the following risk factors: High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Women who have delivered a baby weighing > 9 lb or were diagnosed with GDM Women with polycystic ovarian syndrome Prediabetes as defined by IFG, IGT or A1c on previous testing Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) History of first degree relative with T2DM

1.2 Cardiovascular Risk Factors Established ASCVD Hypertension (blood pressure 140/90 mmHg or on hypertension therapy) HDL cholesterol < 35 mg/dL Triglyceride level > 250 mg/dL LDL cholesterol > 70 and calculated 10 year cardiovascular event risk > 7.5 or on lipid lowering therapy

Shared decision-making with a full discussion of the risks and benefits of treatment and consideration of patient values and preferences.

Shareddecision-making

A recommendation has been made and should be utilized; the benefit outweighs the harms for most patients.

A recommendation has been made and may be utilized; the benefit is felt to potentially outweigh the harms for most patients.

A recommendation against has been made; the harms outweigh the benefits for most patients.

Diagnosis of T2DM A1c 6.5% FPG 126 mg/dL Symptomatic and casual plasma glucose 200 mg/dL

1.5

Return to Table of Contents

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Management Algorithm

Diagnosis and Management of Type 2 Diabetes Mellitus in Adults Sixteenth Edition/July 2014


Treatment goals not metModify treatment; if applicable use appropriate related guideline Assess patient adherence/capacity Evaluate for depression Insulin management

Does the patient need inpatient diabetes

management?

Patient diagnosed with T2DM






Inpatient diabetes management

3

yes

Personalize goals to achieve glycemic control with a hemoglobin A1c in the

range of < 7 or 8% based on the risks and benefits for each patient

4


Recommend education and self-management, as appropriate5.1 Nutrition therapy5.2 Physical activity5.3 Weight management5.4 Bariatric surgery*5.5 General diabetes self-management education5.6 Foot care education5.7 Tobacco cessation

* Bariatric surgery may be considered but is not a treatment strategy for all patients

5

Initiate metformin as first-line pharmacotherapy for patients with

T2DM, unless medically inappropriate

6

Review all cardiovascular risk factors and assessthe need for the following management:7.1 Antihypertensive therapy7.2, 7.3 Statin therapy7.4 Aspirin therapy

See Cardiovascular Risk Management algorithm

7

8

no

Ongoing management and follow-up

9

Maintain treatment goals and address complications

yes

Are treatment goals met?



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Cardiovascular Risk Management Algorithm



Initiate a high-intensity statin therapy

For additional information, refer to the ICSI Lipid Management in Adults guideline

7.2a






Review all cardiovascular risk factors and assess the need for the following management:7.1 Antihypertensive therapy7.2, 7.3 Statin therapy7.4 Aspirin therapy

7

Antihypertensive therapy Aspirin therapy

Blood pressure 140/90 mmHg?

Established ASCVD or LDL> 190 mg/dL?

Initiate antihypertensive medication and treat to a goal of

< 140/90 For additional information, refer to the ICSI Diagnosis and Management of Hypertension guideline

yes

7.1

10-year ASCVD risk 7.5%?

no

Initiate a high-intensity statin

therapy


yes

LDL 70 mg/dL and < 75 years old?

Initiate a moderate- to high-intensity statin therapy

For additional information, refer to the ICSI Lipid Management in Adults guideline

yesShared

decision-making

Established ASCVD?

Initiate aspirin therapyfor secondary prevention

yes

Consider aspirin therapy for primary

prevention

yes

Statin therapy

no

Consider statin therapy and individualize

decisions based on risk factors and patient

preference

no

Assess for other cardiovascular risk factors and return to the Management algorithm

Patient > 40 years old?

no

no

7.2b

7.3

7.4b

7.4a

yes


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Table of Contents


Work Group LeaderBruce Redmon, MDEndocrinology, University of Minnesota

Work Group MembersHealthPartners Medical Group and Regions HospitalDavid Caccamo, MDFamily MedicineRyan Michels, PharmD, BCPSPharmacyPatrick O'Connor, MDFamily MedicineJulie Roberts, MS, RD, CDEHealth EducationJoAnn Sperl-Hillen, MDInternal MedicineMayo ClinicSteve Smith, MDEndocrinologyOlmsted Medical CenterPenny Louise Flavin, DNP, RN, CNPFamily Practice

ICSI StaffCassie MyersProject ManagerLinda Setterlund, MA, CPHQ Clinical Systems Improvement Facilitator

Algorithms and Annotations ........................................................................................ 1-41Algorithm (Diagnosis) ................................................................................................................ 1Algorithm (Management) ........................................................................................................... 2Algorithm (Cardiovascular Risk Management) .......................................................................... 3Evidence Grading ........................................................................................................................ 5Foreword

Introduction ........................................................................................................................... 6Scope and Target Population ................................................................................................. 6Aims ...................................................................................................................................... 7Clinical Highlights ................................................................................................................ 7Implementation Recommendation Highlights ...................................................................8-9Related ICSI Scientific Documents ....................................................................................... 9Definition/Abbreviations ....................................................................................................... 9

Annotations .......................................................................................................................... 10-41Annotations (Diagnostic) ............................................................................................... 10-12Annotations (Management) ............................................................................................ 13-33Annotations (Cardiovascular Risk Management) .......................................................... 33-41

Quality Improvement Support .................................................................................. 42-58Aims and Measures ..............................................................................................................43-44

Measurement Specifications ...........................................................................................45-55Implementation Tools and Resources ....................................................................................... 56Implementation Tools and Resources Table .........................................................................57-58

Supporting Evidence..................................................................................................... 59-77References ............................................................................................................................60-70Appendices ...........................................................................................................................71-77

Appendix A Order Set: Subcutaneous Insulin Management ....................................... 71-73Appendix B Treatment of Diabetic Nephropathy .............................................................74Appendix C Using a Semmes-Weinstein Monofilament to Screen the Diabetic Foot for Peripheral Sensory Neuropathy ..........................................................75Appendix D Using a Tuning Fork to Screen the Diabetic Foot for

Peripheral Neuropathy .................................................................................................... 76Appendix E Sample of Hypoglycemia Protocol .............................................................. 77

Disclosure of Potential Conflicts of Interest .......................................................... 79-80Acknowledgements ........................................................................................................ 81-82Document History and Development ...................................................................... 83-84

Document History ..............................................................................................................83ICSI Document Development and Revision Process .........................................................84


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Evidence Grading Literature SearchThis guideline is based on a systematic evidence review evaluating literature published on type 2 diabetes mellitus (T2DM). The literature search was divided into two stages to identify systematic reviews, (stage I) and randomized controlled trials, meta-analysis and other literature (stage II). Literature search terms used for this revision are below and include literature from January 1, 2004, through May 31, 2014. Hand searching of identified articles and work group submission was also undertaken. For additional information on literature searched, see Additional Resources.

The databases searched included PubMed and Cochrane. The search was limited to only studies in the English language. The following searches were performed and utilized in this document in regards to T2DM: screening, diagnosis, diagnostic testing, risk factors, bariatric surgery, blood pressure, lipid management, insulin, nutrition therapy, glycemic control, weight loss, metformin, self-management and education.

GRADE MethodologyFollowing a review of several evidence rating and recommendation writing systems, ICSI has made a decision to transition to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

GRADE has advantages over other systems including the current system used by ICSI. Advantages include:

Developed by a widely representative group of international guideline developers

Explicit and comprehensive criteria for downgrading and upgrading quality of evidence ratings

Clear separation between quality of evidence and strength of recommendations that includes a transparent process of moving from evidence evaluation to recommendations

Clear, pragmatic interpretations of strong versus weak recommendations for clinicians, patients and policy-makers

Explicit acknowledgement of values and preferences and

Explicit evaluation of the importance of outcomes of alternative management strategies



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ForewordIntroduction

Diabetes is a chronic disease, that afflicts approximately 26.9% of U.S. residents aged 65 years and older. 1.9 million are diagnosed with diabetes every year, and an additional 7.0 million go undiagnosed and untreated (Centers for Disease Control, 2011). More than 1 in 5 health care dollars in the U.S. goes to the care of people with diagnosed diabetes, costing $245 billion dollars annually (American Diabetes Association, 2012).

Appropriate medication management targeting glycemic control, hypertension, and lipid management is important for reducing morbidity and mortality, and improving long-term quality of life for patients diagnosed with type 2 diabetes mellitus (T2DM). Lifestyle changes such as nutrition therapy, weight loss, increased exercise, and appropriate education and self-management strategies are pivotal to improved outcomes. Inadequate access to care for chronic disease management as well as the cost of medication can contribute to poor control of T2DM and associated cardiovascular risk factors.

In the current iteration of this guideline, we have focused on the importance of appropriate identification and diagnosis, followed by effective approaches to lifestyle management and pharmacologic therapy. Due to the high percentage of the U.S. population that is diagnosed with diabetes and the effect diabetes has on other comorbidities, appropriate management will improve the patient's experience of care and the health of the population, reducing office visits, emergency department visits, cardiovascular complications. Other related conditions will in turn reduce the total cost of care.


Scope and Target PopulationThis guideline provides a comprehensive approach to the diagnosis and management of T2DM in adults ages 18 and older. Management recommendations will include nutrition therapy, physical activity, self-management approaches and pharmacologic therapy, as well as the prevention and diagnosis of diabetes-associated complications and risk factors.

The management of gestational diabetes and T2DM in patients who are pregnant is excluded from the scope of this guideline. Oral agents do not have Food and Drug Administration approval for use in pregnancy. Additionally, the glycemia goals used are different in pregnancy and require more aggressive treatment. Please refer to the ICSI Routine Prenatal Care guideline for information relating to gestational diabetes and T2DM in patients who are pregnant.

The diagnosis and management of type 1 diabetes is not included in this guideline.



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AimsNote: a multifactorial intervention targeting hyperglycemia and cardiovascular risk factors in individuals with diabetes is most effective. Both individual measures of diabetes care, as well as comprehensive measures of performance on broader sets of measures, are recommended. A randomized controlled trial has shown a 50% reduction in major cardiovascular events through a multifactorial intervention targeting hyperglycemia, hypertension, dyslipidemia, microalbuminuria, aspirin and ACE inhibitor use in individuals with microalbuminuria (Gaede, 2003).

Goals for A1c, low-density lipoprotein and other diabetes measures should be personalized, and lower goals for A1c and low-density lipoprotein than those included here in the priority aims and measures may be clini-cally justified in some adults with T2DM. However, efforts to achieve A1c below 7% may increase risk of mortality, weight gain, hypoglycemia and other adverse effects in many patients with T2DM. Therefore, the aims and measures listed here are selected carefully in the interests of patient safety.

Outcome Measures

1. Diabetes Optimal Care: Increase the percentage of patients ages 18-75 years with T2DM mellitus who are optimally managed. (Education and Self-Management)

2. Management of T2DM in high-risk patients (Trial measure): Decrease the percentage of adult patients ages 18-75 with T2DM mellitus with poorly controlled glucose and cardiovascular risk factors. (Cardiovascular Risk)

3. Lifestyle modification and nutrition therapy increase the percentage of patients ages 18-75 years newly diagnosed with T2DM who are advised about lifestyle modification and nutrition therapy.

4. Medication Management increase the percentage of patients with T2DM who are on appropriate medication management.


Clinical Highlights Education and self-management support is necessary for people with prediabetes and T2DM to manage

his/her disease. (Prediabetes, General Diabetes and Self-Management Education)

Focus on cardiovascular risk reduction (blood pressure control, low-density lipoprotein cholesterol lipid control primarily with statin use, aspirin use and tobacco cessation). (Cardiovascular Risk, General Diabetes and Self-Management Education)

A1c levels should be individualized to the patient. (Glycemic Control)

Aggressive blood pressure control is just as important as glycemic control. Systolic blood pressure level should be the major factor for detection, evaluation and treatment of hypertension. The use of two or more blood pressure-lowering agents is often required to meet blood pressure goal. (Cardiovascular Risk)

Prevent microvascular complications through annual or biannual eye exams, foot risk assessments and foot care counseling, and annual screening for proteinuria. (Ongoing Management)

Initial therapy with lifestyle treatment and metformin is advised, unless contraindicated. (General Diabetes and Self-Management Education, Pharmacotherapy)


Diagnosis and Management of Type 2 Diabetes Mellitus in Adults Foreword Sixteenth Edition/July 2014


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Implementation Recommendation HighlightsThe following system changes were identified by the guideline work group as key strategies for health care systems to incorporate in support of the implementation of this guideline.

The implementation of T2DM clinical guidelines at medical groups and clinics is a complex and challenging task. However, a number of key processes have been shown to accelerate effective clinical guideline imple-mentation and care improvement (Sperl-Hillen, 2005). These overlapping care elements can be categorized at the medical group and clinician levels:

Essential elements at the medical group level:

- Leadership. Medical group leaders must communicate the need for change in clinical practice patterns and consistently identify improvement priorities.

- Resources. Resources adequate to the task at hand will be needed to assure the success of a change effort. Resources may include staff time, money and provision of tools (such as elec-tronic medical records) to support care improvement.

- Select specific improvement goals and measures. For most chronic diseases, including diabetes, the most efficient improvement strategy is to focus on a limited number of specific improvement goals. These may be based on observed gaps in care, potential clinical impact, cost considerations or other criteria (O'Connor, 2005a). In T2DM, focusing on glycemic control, lipid control and blood pressure control is a strategy that has been shown to be effective in preventing up to 53% of heart attacks and strokes, the leading drivers of excess mortality and costs in adults with diabetes (Gaede, 2003).

- Accountability. Accountability within the medical group is a management responsibility, but external accountability may also play an important enhancing role to motivate sustained efforts to implement guidelines and improve care. Examples of external accountability include participa-tion in shared learning activities or public reporting of results (such as in pay-for-performance or the Minnesota Community Measures Project).

- Prepared practice teams. The medical group may need to foster the development of prepared practice teams that are designed to meet the many challenges of delivering high-quality chronic disease care.

Essential elements at the clinic level:

- Develop "smart" patient registries. These are registries that are designed to identify, auto-matically monitor, and prioritize patients with diabetes based on their risk, current level of control, and possibly patient readiness-to-change.

- Assure "value-added" visits. These are office visits or other patient encounters (by phone, e-mail, etc.) that include intensification of treatment if the patient has not yet reached his/her evidence-based clinical goals. Failure of clinicians and patients to intensify treatment when indicated (referred to as "clinical inertia") is a key obstacle to better diabetes care (O'Connor, 2005a; O'Connor, 2005b; O'Connor, 2003). Previsit planning and best practice prompts may help to increase the efficiency of patient visits and remind clinicians of needed tests and care.

- Develop "active outreach." These are strategies to reach patients with chronic disease who have not returned for follow-up or for other selected elements of care. Outreach strategies that enhance the likeliness of a future provider encounter that addresses one of the barriers to patient activation (discussed below) may be more effective. Simple reporting of lab test results or care suggestions through the mail may be ineffective at addressing these barriers.




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- Emphasize "patient activation" strategies. These may include diabetes education and other actions designed to sustain engagement of patients with his/her diabetes care. Many patients with diabetes either (a) do not really believe they have diabetes, or (b) do not really believe that diabetes is a serious disease, or (c) lack motivation for behavioral change, or (d) do not believe that recommended treatments will make a difference to their own outcomes. For care to be effective, these issues must be addressed for many patients (O'Connor, 1997).


Related ICSI Scientific DocumentsGuidelines

Healthy Lifestyles

Diagnosis and Treatment of Hypertension

Lipid Management in Adults

Major Depression in Adults in Primary Care

Preventive Services for Adults

Prevention and Management of Obesity for Adults


Definition/AbbreviationsClinician All health care professionals whose practice is based on interaction with and/or treatment of a patient.

FPG fasting plasma glucose

OGTT Oral glucose tolerance test

T2DM type 2 diabetes mellitus



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Algorithm AnnotationsDiagnostic Algorithm Annotations1. Assessment and Diagnosis of T2DM1.1 BMI and Associated Risk Factors of T2DM

Recommendation Quality of Evidence and Strength of Recommendation

A clinician may test asymptomatic patients for T2DM when the patient has a BMI to 25 kg/m2) and has one or more additional risk factors (see below), regardless of age.

High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)

Women who have delivered a baby weighing > 9 lb. or were diagnosed with GDM Women with polycystic ovarian syndrome Prediabetes as defined by IFG, IGT or A1c on previous testing Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) History of first-degree relative with T2DM

Quality of Evidence: Low

Strength of Recommendation: Weak

Benefits: Patients can develop T2DM without symptoms, and early detection of diabetes allows for earlier implementation of lifestyle modifications and glucose control, and has a legacy effect that can reduce or prevent complications including retinopathy, neuropathy, nephropathy, peripheral vascular disease, and microvascular and cardiovascular disease. Targeted testing for patients of any age who are overweight or obese and have additional risk factors has shown to be cost effective. Harms: It is unclear for patients with prediabetes that there is a full understanding of which patients will progress to T2DM. Some patients may have increased testing and treatment without benefit, and having the diagnosis of diabetes could potentially have negative psychosocial and economic ramifications for individuals. Benefits-Harms Assessment: Diabetes screening is potentially costly and has not been proven to result in improved patient outcomes. However, the condition is common, serious, and a cause of serious microvascular and macrovascular health complications. Selective testing of high-risk individuals can reduce the costs compared to universal testing. There are no significant harms to the health of individuals who undergo testing. Relevant Resources: Casagrande, 2013; Colosia, 2013; Waugh, 2013; Ackermann, 2011; Li, 2010; Gregg, 2004

Return to Algorithm Return to Table of Contents

1.2 Cardiovascular Risk

Recommendation Quality of Evidence and Strength

of Recommendation A clinician may screen asymptomatic patients for T2DM who have increased cardiovascular risk (see below), regardless of age.

Established ASCVD Hypertension (blood pressure 140/90 mmHg or on hypertension therapy) HDL cholesterol < 35 mg/dL Triglyceride level > 250 mg/dL LDL cholesterol > 70 and calculated 10-year cardiovascular event risk > 7.5% or on lipid-lowering

therapy



Benefits: Patients can develop T2DM without symptoms, and early detection of diabetes allows for earlier implementation of lifestyle modifications and glucose control, and has a legacy effect that can reduce or prevent complications including retinopathy, neuropathy, nephropathy, peripheral vascular disease, and other microvascular and macrovascular health complications, and reduce the risk of coronary events. Targeted testing for patients with hypertension has show to be cost effective. Harms: It is unclear for patients with prediabetes that there is a full understanding of which patients will progress to T2DM. Some patients may have increased testing and treatment without benefit, and having the diagnosis of diabetes could potentially have negative psychosocial and economic ramifications for individuals. Benefits-Harms Assessment: Appropriate management of cardiovascular disease and diabetes is supportive of improved mortality and reduction in CVD events with no significant harms to the health of individuals who undergo screening. Relevant Resources: Casagrande, 2013; Colosia, 2013; Waugh, 2013; Rahman, 2012; Ackermann, 2011; American Diabetes Association, 2010; Li, 2010; U.S. Preventive Services Task Force, 2008




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1.3 Screening


A clinician should not screen for T2DM in asymptomatic patients without additional risk factors. Quality of Evidence: Low

Strength of Recommendation: Strong

Benefits: Universal screening incurs substantial costs for initial screening procedures, and many individuals would need to undergo additional testing procedures to confirm or refute the initial screening test, leading to both testing costs and economic costs, such as time away from work or other productive activities. Two randomized trials failed to show a benefit of screening for diabetes on overall mortality. One of these trials found little evidence of benefits from screening on clinical measures of diabetic complications, cardiovascular health, medication use or functional status. In this trial, screening for diabetes appeared to shorten the time to diagnosis of diabetes by only about three years. Harms: Universal screening would be expected to maximize the number of people diagnosed with diabetes early in their disease process. This would allow for early implementation of therapeutic measures to control hyperglycemia, resulting in a hopefully cost-effective intervention to reduce the incidence of later diabetes-related complications. A randomized trial of screening for diabetes found no evidence of adverse effects of screening on physical or emotional health of screened compared to unscreened individuals. Benefits-Harms Assessment: The absence of clinical benefit as shown in data from randomized trials and increase in costs would argue against a recommendation for universal screening in unselected populations or populations judged to be at low risk for diabetes. Relevant Resources: Waugh, 2013; Rahman, 2012; Simmons, 2012; Norris, 2008

Return to Algorithm Return to Table of Contents1.4 Diagnostic Testing for T2DM and 1.5 Diagnosis of T2DM


A clinician should diagnose a patient with T2DM through the use of an A1c test with a threshold 6.5%, FPG 126 mg/dL or a two-hour plasma glucose 200 mg/dL on a 75g OGTT. Additionally, if a patient has symptoms of hyperglycemia and casual plasma glucose 200 mg/dL, diabetes may be diagnosed.



Benefits: A1c testing does not require fasting like other methods of testing, which may increase the likelihood that a patient will undergo testing for T2DM and have appropriate diagnosis and treatment. A1c testing also measures chronic glucose exposure over a two- to three-month period and is less influenced by internal factors including stress and/or illness than FPG or OGTT. Both OGTT and FPG are not influenced by abnormal red cell turnover conditions, and both allow for clear guidelines of diagnosis, especially for those who have normal fasting blood sugars. Harms: A1c testing may miss a portion of the population that would be diagnosed with T2DM using FPG or OGTT criteria, including those that have an abnormal hemoglobins or conditions that affect red blood cell turnover. There may also be racial or ethnic differences in the relationship between glycemia and A1c levels, and these could result in false-negatives or false-positives. FPG and OGTT both require fasting, which may reduce screening rates, and decrease appropriate diagnosis and management due to convenience. The two-hour OGTT is time consuming in both patient fasting and administration. Benefits-Harms Assessment: The general acceptance of all three testing methods and the specific thresholds are well established. Providing a choice of testing methods is likely to increase the likelihood that appropriate patients are tested for diabetes, minimize cost and inconvenience, and allow clinicians to individualize test selection based on individual patient characteristics. Relevant Resources: Waugh, 2013; American Diabetes Association, 2010; Cowie, 2010; Kumar, 2010; Olson, 2010, International Expert Committee, 2009; Droumaguet, 2006

Supplemental Information

In the absence of unequivocal hyperglycemia, an abnormal A1c, fasting glucose or oral glucose tolerance test result that meets criteria for diabetes should be confirmed by repeat testing before assigning a diagnosis of T2DM.

It is preferable that the same test be repeated for confirmation of diabetes. There may be cases in which two different tests are available (e.g., A1c and fasting glucose). If both tests meet diagnostic criteria for diabetes, a diagnosis of diabetes can be made.


Diagnosis and Management of Type 2 Diabetes Mellitus in Adults Algorithm Annotations Sixteenth Edition/July 2014


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If two different tests are available and are discordant (e.g., A1c > 6.5%, fasting glucose < 126 mg/ dL), then the test whose result is above the diagnostic threshold should be repeated. If it is again above the diagnostic threshold on repeat testing, a diagnosis of diabetes can be assigned.


2. Diagnosis of PrediabetesPrediabetes. Prediabetes is defined as hyperglycemia that is not sufficient to meet the diagnostic criteria for diabetes, but that is associated with an increased risk of progression to T2DM. Diagnosis of prediabetes is made when an individual meets one or more of the following criteria:

A1c 5.7-6.4%

Fasting plasma glucose of 100 mg/dL to 125 mg/dL

Oral glucose tolerance test two-hour plasma glucose: 140 mg/dL to 199 mg/dL


2.1 Treatment to Prevent or Delay Progression to T2DMPatients who are identified with prediabetes should be referred for education and life-style interventions to a qualified health professional (which may include clinician, dietitian, nursing staff and pharmacist).

Intensive lifestyle change or programs have been proven effective in delaying or preventing the onset of diabetes by about 50-58%. Effective lifestyle changes include setting achievable goals, obtaining weight loss when needed (between 5-10% of total body weight is recommended), and increasing physical activity to a minimum of 150 minutes per week (Tuomilehto, 2001).

Patients with IGT, IFG or an A1c should be referred to an effective ongoing support program targeting weight loss of 7% of body weight and increasing physical activity to at least 150 minutes per week of moderate activity such as walking.

Metformin therapy for prevention of T2DM may be considered in those patients meeting criteria for prediabetes.

At least annual monitoring for the development of diabetes in those with prediabetes may be utilized.

Screening for and treatment of modifiable risk factors for CVD are suggested.

Patients who respond to lifestyle interventions:

Annual follow-up and reassessment of risks for developing diabetes (American Diabetes Association, 2014; Chiasson, 2002; Heart Outcomes Prevention Evaluation Study Investigators, 2002; Kelley, 2002; Eriksson, 1999)

Patients who are high risk and not responding to lifestyle interventions:

Intensify education and counseling on lifestyle interventions. Lifestyle change remains the preferred method to prevent diabetes.

Health care clinicians should follow patients diagnosed with prediabetes on an annual basis to monitor his/her progress and review treatment goals (American Diabetes Association, 2014).




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Management Algorithm Annotations3. Inpatient Diabetes Management

Inpatient care may be appropriate in the following situations (American Diabetes Association, 2004d):

Elderly patients with infection or illness, weight loss, dehydration, polyuria or polydipsia

Life-threatening acute metabolic complications of diabetes:

- Hyperglycemic hyperosmolar state with impaired mental status, elevated plasma osmolaity that includes plasma glucose greater than 600 mg/dL

- Diabetic ketoacidosis with a plasma glucose greater than 250 mg/dL, arterial pH less than 7.30 and serum bicarbonate level less than 15 mEq/L and the presence of moderate ketonuria and/or ketonemia

- Hypoglycemia with neuroglycopenia that includes blood glucose less than 50 mg

Uncontrolled insulin-requiring diabetes during pregnancy

Surgery, infection, steroids if these conditions cause significant hyperglycemia and rapid initiation of rigorous insulin is needed

Hospitalized patients with diabetes suffer increased morbidity, mortality, length of stay and other related hospital costs compared to non-hyperglycemic inpatients. These negative outcomes are observed more frequently in hospitalized patients with newly discovered hyperglycemia. Hyperglycemia is an independent marker of inpatient mortality in patients with undiagnosed diabetes (Umpierrez, 2002).

Hyperglycemia has been associated with increased infection rates and poorer short-term and long-term outcomes in critically ill patients in the intensive care unit, post-myocardial infarction and post-surgical settings. Earlier studies supported that aggressive glucose management in medical and surgical patients improves outcomes (Van den Berghe, 2001). More recently, intensive management has been linked to increased hypoglycemia and increased mortality in a subset of patients including those with a long history of diabetes and cardiovascular disease (NICE-SUGAR Study Investigators, The, 2009).

The following are suggestions for the inpatient setting (American Diabetes Association, 2014; Clement, 2004):

Insulin therapy with intravenous insulin in critically ill patients (Van den Berghe, 2001)

Oral glycemic agents may need to be held or the dose adjusted if the patient is hospitalized

Use of scheduled insulin, with basal coverage (improves glucose control compared to sliding scale coverage alone)

For insulin-deficient patients, despite reductions or the absence of caloric intake, basal insulin must be provided to prevent diabetic ketoacidosis

Target preprandial plasma glucose levels to 90-140 mg/dL (American Diabetes Association, 2014; NICE-SUGAR Study Investigators, The, 2009; American Diabetes Association, 2004b; Clement, 2004; Garber, 2004)

Target random plasma glucose to less than 180 mg/dL (American Diabetes Association, 2014; Holman, 2009; NICE-SUGAR Study Investigators, The, 2009; American Diabetes Association, 2004b; Clement, 2004; Garber, 2004)

A protocol should be utilized for patients with hypoglycemia < 70 mg/dL (American Diabetes Association, 2014; Cryer, 2003)




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Establishing a multidisciplinary team that sets and implements institutional guidelines, protocols and standardized order sets for the hospital results in reduced hypoglycemic and hyperglycemic events

Other considerations include (Clement, 2004):

For patients who are alert and demonstrate accurate insulin self-administration and glucose moni-toring, insulin self-management should be allowed as an adjunct to standard nurse-delivered diabetes management.

Patients with no prior history of diabetes who are found to have hyperglycemia (random fasting blood glucose greater than 125 mg/dL or random glucose of 200 mg/dL or more) during hospitaliza-tion should have follow-up testing for diabetes within one month of hospital discharge (Umpierrz, 2002).

Types of InsulinBased on outpatient studies, consider insulin Glargine or Detemir as the basal insulin (there are limited inpatient studies to date). In studies comparing Glargine to NPH, the risk of nocturnal hypoglycemia was reduced (Wang, 2003; Yki-Jarvinen, 2000). Treatment with insulin Detemir resulted in more predictable glycemic control than NPH insulin (Vague, 2003).

Consider using rapid-acting insulin analogs (e.g., lispro, aspart, glulisine instead of regular insulin) unless the patient is to have nothing by mouth or is on continuous feedings. Initial studies comparing rapid-acting insulin with human regular insulin show rapid-acting insulins to be more effective at reducing the peak postprandial glucose concentration (Reynolds, 2004). They may also lower the demand for endogenous insulin, provide superior postprandial glycemic control, and cause fewer hypoglycemic episodes requiring medical intervention (Rave, 2006; Pettitt, 2003; Gerich, 2002).

Insulin lispro, glulisine and aspart have similar pharmacokinetics; they have an earlier onset and peak of action than regular insulin. Peak action usually occurs at one hour with a duration of three to four hours, while regular insulin has a peak action of two to four hours and a duration of six to eight hours. Lispro, glulisine and aspart may then reduce the occurrence of late postprandial hypoglycemia compared to regular insulin (Guerci, 2005; John, 2004).

Insulin Dosing ScheduleInsulin dosing schedules must be individualized based on a variety of factors, including the severity of diabetes, oral intake, severity of illness and other concurrent diabetic medication. It is not feasible to design a single algorithm for determining an insulin regimen in every patient. The following information provides general guidance in determining initial insulin doses.

Healthy, non-diabetic people are estimated to secrete approximately 0.4-1.0 units of insulin/kg body weight per day (Polonsky, 1988a; Davidson, 1986). Approximately 50% of this insulin is secreted as basal insulin and 50% as postprandial boluses following meals (Polonsky, 1988b). Typical daily insulin doses for people with diabetes range from 0.5 to 0.7 units/kg per day. In the United Kingdom Prospective Diabetes Study of people with T2DM, the median daily insulin dose for people in the intensive insulin treatment arm of the study after a diabetes duration of approximately 12 years was 36 units/day (UK Prospective Diabetes Study Group, 1998).

Fifty percent of subjects were receiving between 23 and 53 units of insulin per day. The average weight of subjects was 75 kg, so the "average" daily insulin requirement was about 0.5 units/kg (UK Prospective Diabetes Study Group, 1998). Therefore, in initiating subcutaneous insulin in a hospitalized patient who is eating meals, a total daily insulin dose of 0.6 units/kg is probably reasonable (Clement, 2004). Modification




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can be made based on clinical judgment for factors such as severity of illness, fragility, renal function, body weight, expected nutritional intake and medication effects (e.g., glucocorticoid medications).

Based on the normal physiology of insulin release and experience with outpatient regimens for managing diabetes with subcutaneous insulin, it has been recommended that inpatient subcutaneous insulin regimens comprise three components (Clement, 2004):

A basal insulin component

A prandial insulin component (for patients eating meals)

A correction, sometimes referred to as "supplemental," insulin component used to treat hypergly-cemia before or between meals (Clement, 2004)

In a small, randomized trial comparing a basal/prandial insulin regimen to a traditional sliding scale insulin regimen in hospitalized patients with T2DM, the basal/prandial insulin regimen resulted in improved glycemic control during the hospitalization. Hospital length-of-stay or incidences of hypoglycemia did not differ between the basal/prandial insulin regimen or the sliding scale insulin regimen (Umpierrez, 2007).

Basal insulin

Typical approach is to give 40-50% of the estimated total daily insulin dose as the basal insulin component. Common basal regimens include one injection per day of Glargine insulin, usually given at bedtime or twice daily; Detemir insulin given once daily in the evening or given twice daily; twice-a-day injections of NPH insulin, given at breakfast and either at supper or bedtime; or once-a-day NPH insulin given at bedtime (Vague, 2003). Basal insulin would generally be appropriate for any patient being managed with subcutaneous insulin, whether eating meals, nothing by mouth or receiving nutrition as continuous enteral feeding or total parenteral nutrition (TPN) (Clement, 2004).

Prandial insulin

For patients eating meals, several approaches have been suggested to initiate a prandial insulin regimen:

Divide 50% of the estimated daily insulin requirement into three equal insulin doses given before the three meals.

Estimate the prandial insulin dose before each meal as 10-20% of the estimated daily insulin requirement.

Count the carbohydrate content of the meal (one carbohydrate unit = 15 gm of meal carbo-hydrate), and determine the prandial insulin dose as a set number of units of insulin per meal carbohydrate unit.

Insulin doses based on grams of carbohydrates consumed.

Typical insulin requirements using this last approach are one to two units of insulin per carbohydrate unit (Clement, 2004).

It is recommended that prandial insulin be given as a rapid-acting insulin analog within 0-15 minutes of the meal (Clement, 2004). Prandial insulin replacement has its main effect on peripheral glucose disposal into muscle. Also referred to as "bolus" or "mealtime" insulin, prandial insulin is usually administered before eating. There are occasional situations when this insulin may be injected immediately after eating, such as when it is unclear how much food will be eaten. In such situations, the quantity of carbohydrates taken can be counted and an appropriate amount of rapid-acting analog can be injected (Clement, 2004).

Patients who are not eating meals will not typically require a prandial insulin component, although they may need periodic correction insulin.




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Correction (supplemental) insulin

Correction dose insulin is given in addition to the scheduled basal and prandial insulin in order to correct hyperglycemia. For patients eating meals, it is typically given with meals by simply increasing the rapid-acting insulin dose by an additional amount based on the correction schedule. For patients not eating meals (e.g., nothing by mouth, on continuous enteral feeding, total parenteral nutrition), it is reasonable to give periodic short-acting insulin, either as regular insulin or a rapid-acting analog, based on the correction schedule at four- to six-hour intervals (Guerci, 2005; John, 2004). If rapid-acting insulin is used in this situation, an every-four-hour schedule may be optimal. For regular insulin, a four- to six-hour schedule is reasonable (Clement, 2004).

The correction dose insulin schedule must be individualized for the patient. A typical assumption is that one unit of insulin will lower the blood glucose 50 mg/dL (Hirsch, 2002). An empiric "Rule of 1,700" has been proposed as one way of estimating the insulin correction requirement. This rule estimates that the decrease in glucose in response to one unit of insulin = (1,700/patient's total daily insulin dose) (Davidson, 2003). The "Low," "Medium" and "High" correction schedules included on the order set assume that one unit of insulin will lower the blood glucose by approximately 50, 25 and 15 mg/dL, respectively.

There does not appear to be a consensus whether correction insulin should be given at bedtime. Some experts argue against bedtime correction insulin due to a fear of nocturnal hypoglycemia with short- or rapid-acting insulin given at bedtime (Hirsch, 1995). If correction insulin is given at bedtime, the recommendation is that the correction dose should be reduced (Clement, 2004).

Hyperglycemia induced by corticosteroid therapy is often characterized by predominant postprandial hyper-glycemia with lesser effects on fasting glucose levels. For patients with corticosteroid-induced hypergly-cemia, caution is suggested in prescribing correction dose insulin at bedtime due to the increased risk of nocturnal hypoglycemia (Clement, 2004).

Example:

The following is an example of one possible initial subcutaneous insulin regimen for a hospitalized patient weighing 100 kg with hyperglycemia who is eating meals.

Estimated total daily insulin dose = 100 kg x 0.6 units insulin/kg = 60 units of insulin daily.

Basal: 50% of total daily insulin dose = 30 units given as Glargine or Detemir insulin at bedtime.

Prandial: 50% of total daily insulin dose/3 = 30 units/3 = 10 units of insulin at each meal given as Lispro, Glulisine or Aspart insulin.

Correction schedule: Assuming 1 unit of insulin will drop the blood glucose 50 mg/dL, the "Low" correction schedule on the order set could be used. Using the Rule of 1,700, one would estimate that one unit of insulin = drop in blood glucose of (1,700/60) = 28 mg/dL. In this case, the "Medium" correction schedule might be chosen.

Whatever insulin regimen is initially implemented, it will likely need to be modified over the course of a patient's hospitalization. If a patient is frequently requiring use of the correction schedule, common sense would dictate that either the basal component, prandial component or both need to be modified.

Transition from Intravenous to Subcutaneous InsulinWhen transitioning from intravenous to subcutaneous insulin, it is generally recommended that an initial subcutaneous basal insulin dose of long- or intermediate-acting insulin be given prior to discontinuation of the intravenous insulin (Furnary, 2006). Based on the absorption profiles of longer-acting insulins, admin-istering the first subcutaneous insulin dose two hours prior to stopping the insulin infusion would appear to




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allow sufficient overlap to avoid excessive rebound hyperglycemia when the insulin infusion is discontinued (Furnary, 2006; Clement, 2004).

Determination of the initial basal insulin dose can be made using the guidelines above (e.g., estimating the basal insulin dose as 40-50% of the estimated total daily insulin dose). An alternative method that has been suggested is to estimate the initial basal dose based on the intravenous insulin requirements over a six- to eight-hour period leading up to the transition time. Ideally, this six- to eight-hour period would be a time when the patient was not eating and was not receiving intravenous glucose. The initial basal insulin dose could be calculated as 80% of the estimated 24-hour insulin requirement to provide a margin of safety (Furnary, 2006).

Example:

A patient managed on an intravenous insulin drip is to be transitioned to subcutaneous insulin. Over a recent six-hour period when the patient was not eating and was not receiving intravenous glucose, the patient received a total of 15 units of insulin via the infusion. The estimated 24-hour basal insulin requirement would be 15 x 4 = 60 units. The initial basal insulin dose could be estimated as 80% x 60 units = 48 units.

Often the clinician may want to use a bedtime long-acting insulin (e.g., Glargine insulin) as the subcuta-neous basal insulin, but the transition from intravenous to subcutaneous insulin is planned to occur during the day. In these cases, one option would be to give a one-time dose of NPH insulin by subcutaneous injection to act as a bridge until the regularly scheduled long-acting insulin is given (Clement, 2004). A typical NPH insulin dose might be 40% of the planned long-acting insulin dose.

Example:

Using the example above, the clinician plans to give 48 units of Glargine insulin at bedtime as the basal insulin dose on the transition to subcutaneous insulin. However, the clinician would like to tran-sition the patient to subcutaneous insulin during the day rather than waiting until later in the evening when fewer staff are present. A one-time order for NPH insulin 20 units (40% x 48 units = 19.2 units, round to 20 units) could be written to be given two hours before the insulin infusion is stopped. This intermediate-acting insulin would provide temporary basal insulin coverage until bedtime, when the 48 units of Glargine insulin could be given.

Prandial and correction insulin orders should also be written as appropriate for the patient's situation (eating, on tube feeding, etc.) on transition to subcutaneous insulin. This insulin would then be given in addition to the basal insulin in accordance with the order set.

Medication adherence

Non-adherence with medications can limit the success of therapy and help to explain why a patient is not achieving treatment goals. To screen for non-adherence, clinicians can ask patients open-ended, non-threat-ening questions at each office visit. The assessment should include probes for factors that can contribute to non-adherence (fear of adverse reactions, misunderstanding of chronic disease treatment, depression, cognitive impairment, complex dosing regimens or financial constraints).

Assess the patient's knowledge of his/her condition and his/her expectations for treatment

Assess the patient's medication administration process

Assess the patient's barriers to adherence

Interventions to enhance medication adherence should be directed at risk factors or causes of non-adherence. Interventions may include simplifying the medication regimen, using reminder systems, involving family or caregivers in care, involving multiple disciplines in team care, providing written and verbal medication




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instructions, setting collaborative goals with patients, and providing education about medications (including potential adverse effects) and about diabetes in general (Nichols-English, 2000).

Depression evaluation

There is a substantial increase in the prevalence of depression among people with diabetes as compared to the general adult population (Anderson, 2001). Depression impacts the ability of a person with diabetes to achieve blood glucose control, which in turn impacts the rate of development of diabetes complications (de Groot, 2001; Lustman, 2001).

Identification and management of depression are important aspects of diabetes care. Self-administered or professionally administered instruments, such as PHQ-9, are useful adjuncts to the clinical interview in the identification of depression. The ICSI Major Depression in Adults in Primary Care guideline provides more suggestions for the identification and management of depression. Intervention studies have demonstrated that when depression is treated, both quality of life and glycemic control improve. Counseling may be effec-tive, especially among those who are having difficulty adjusting to the diagnosis of diabetes or are having difficulty living with diabetes. Pharmacotherapy for depression is also effective.

Obstructive sleep apnea

Sleep apnea is a prevalent condition in obese patients with T2DM and is associated with significant comorbidi-ties including hypertension, cardiovascular disease and insulin resistance. Consider referral of symptomatic patients for sleep evaluation. Clinicians should be cognizant of potential obstructive sleep apnea, especially among obese patients (Foster, 2009a; Foster, 2009b).

Referral to an Extended Care TeamDiabetes educator

Consultation with a diabetes educator is suggested if the patient is having difficulty adhering to a nutrition, exercise and medication regimen, and the patient is having difficulty adhering to or accurately completing blood glucose monitoring or may need answers to his/her questions.

Primary care clinician should develop a relationship with a diabetes education program to provide other options for management. The American Diabetes Association publishes a list of recognized educational programs in each state. These programs may be staffed with endocrinologists or primary care clinicians plus diabetes educators including dietitians, nurses and other health care clinicians who are Certified Diabetes Educators or have didactic and experiential expertise in diabetes care and education.

Endocrinologist/nephrologist

Most T2DM management can be managed by a primary care clinician with periodic consultation as needed by an endocrinologist. Consultation with a specialist is suggested if persistent proteinuria, worsening microalbuminuria and elevation in serum creatinine or blood urea nitrogen, or hypertension unresponsive to treatment is seen.

Endocrinologist/neurologist

Consultation with a specialist is suggested if neuropathy progresses and becomes disabling.

Endocrinologist/cardiologist/hypertension specialist

Consultation with a specialist is suggested if blood pressure is refractory to treatment, or the patient has marked associated postural hypotension or symptoms of coronary artery disease.




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Foot care specialist

A consultation with a specialist is suggested if the patient is unable to care properly for his/her own feet, needs prescriptive footwear and/or more serious problems such as foot deformities (e.g., Charcot deformity), infected lesions, and ulcers, deformed nails or thick calluses are present.

Opthalmology/optometry

Retinopathy is estimated to take at least five years to develop after the onset of hyperglycemia begins. Patients with T2DM who generally have had years of undiagnosed diabetes and who have a significant risk of prevalent diabetic retinopathy at time of diabetes diagnosis should have an initial dilated and compre-hensive eye examination soon after diagnosis. Examinations should be performed by an ophthalmologist or optometrist who is knowledgeable and experienced in diagnosing the presence of diabetic retinopathy and is aware of its management. Subsequent examinations are generally repeated annually. Less frequent exams (every two to three years) may be cost effective after one or more normal eye exams, while examina-tions will be required more frequently if retinopathy is progressing (American Diabetes Association, 2014).

Vascular specialist/surgeon

Consider referral if patient has symptoms of peripheral vascular disease such as loss of pulses and/or clau-dication.


4. Glycemic Control and A1c Goals


A clinician should personalize goals with patients diagnosed with T2DM to achieve glycemic control with a hemoglobin A1c < 7% to < 8% depending on individual patient factors.

Quality of Evidence: High


Benefits: Achieving near-normal glycemic control lowers risk of diabetes microvascular complications such as retinopathy, nephropathy and amputations. Achieving A1c of 6.9 to 7.9% may also significantly reduce macrovascular complications based on Steno-2 and UKPDS data. Harms: Near-normal glycemic control (A1c around 6.4 to 6.5%) achieved through intensive pharmacotherapy appears to have less benefit for major CV events (ACCORD ADVANCE VADT) and in one large trial significantly increased mortality 20% (ACCORD). In some patients, aggressive pharmacotherapy with insulin, sulfonylureas or certain other agents may lead to weight gain and severe hypoglycemia. The long-term cardiovascular safety of agents other than metformin and human insulins has yet to be established. Benefits-Harms Assessment: Therefore, to optimize the balance between benefits and harms for a given patient, personalization of glycated hemoglobin (A1c) goals in the range of < 7% to < 8% is recommended. Relevant Resources: Hemmingsen, 2013; Callaghan, 2012; Anderson, 2011; Action to Control Cardiovascular Risk in Diabetes Study Group, The, 2008; ACCORD, 2010b; Ismail-Beigi, 2010; Duckworth, 2009; NICE Sugar Study Investigators, The, 2009; Ray, 2009; Turnbull, 2009; Abraira, 2008; ADVANCE, 2008; Gaede, 2008; Holman 2008a

Supplemental InformationFor patients with T2DM, an A1c goal of less than 8% may be more appropriate than an A1c goal of less than 7%, when including the following factors:

Known cardiovascular disease or high cardiovascular risk, and may be determined by the Framingham or ACC/AHA Cardiovascular Risk Calculator, or alternatively as having two or more cardiovascular risks (BMI > 30, hypertension, dyslipidemia, smoking and microalbuminuria)

Inability to recognize and treat hypoglycemia, including a history of severe hypoglycemia requiring assistance

Inability to comply with standard goals, such as polypharmacy issues




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Limited life expectancy or estimated survival of less than 10 years.

Cognitive impairment.

Extensive comorbid conditions such as renal failure, liver failure and end-stage disease complica-tions.

A multifactorial approach to diabetes care that includes emphasis on blood pressure, lipids, glucose, aspirin use and non-use of tobacco will maximize health outcomes far more than a strategy that is limited to just one or two of these clinical domains (American Diabetes Association, 2014; Duckworth, 2009; Gaede, 2008; Holman, 2008a).

Multifactorial approach

The benefits of a multifactorial approach to diabetes care are supported by the results of the Steno-2 Study of 160 patients with T2DM and microalbuminuria. Multifactorial interventions achieved a 50% reduction in mortality and significant reduction in microvascular complications five years after ending a 7.8-year multifactorial intervention that achieved A1c of 7.8%, low-density lipoprotein 83 mg/dL, blood pressure 131/73, compared to a conventional group that achieved A1c 9%, low-density lipoprotein 126 mg/ dL and blood pressure 146/78 (Gaede, 2008). Results of this study are consistent with the need for reasonable blood glucose control with emphasis on blood pressure and lipid management.

Microvascular/macrovascular complications

Follow-up data from the United Kingdom Prospective Diabetes Study of newly diagnosed patients with T2DM confirm major macrovascular and microvascular benefits of achieving A1c in the 7.1 to 7.3% range, versus A1c of about 8% in the comparison groups (Holman, 2008a). The United Kingdom Prospective Diabetes Study main trial included 3,867 newly diagnosed T2DM patients and showed over a 10-year period a 25% decrease in microvascular outcomes with a policy using insulin and sulfonylureas that achieved a median A1c of 7.1%, compared to 7.9%. A subgroup of obese patients (n=1,704) treated with metformin and achieving a median A1c of 7.3% showed greater advantages over conventional treatment: a 32% reduction of diabetes-related end points (P=0.002), a 42% reduction of diabetes-related deaths (P=0.017), and a 36% reduction of all-cause mortality (P=0.011) (UK Prospective Diabetes Study Group, 1998b).

Several reported clinical trials have evaluated the impact of A1c less than 7% on macrovascular and microvascular complications of T2DM. These studies the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Action in Diabetes and Vascular Disease: Preferax and Diamcron Modified Release Controlled Evaluation (ADVANCE), and VADT Trials are the first that have ever achieved and maintained A1c less than 7% in his/her intensive treatment patients.

Cardiovascular risk

In the ACCORD Trial, excess mortality in the intensive group (A1c mean 6.4% vs. standard group A1c 7.5%) forced the safety board to discontinue the intensive treatment arm earlier than planned (Action to Control Cardiovascular Risk in Diabetes Study Group, The, 2008). There was one excess death for every 90 patients in the intensive group over a 3.5-year period of time. In the ADVANCE trial, intensive group patients achieved A1c 6.5% (vs. 7.5% in standard group) but had no reduction in cardiovascular complications or events. In the VADT trial, intensive group patients achieved A1c of 6.9% but had no significant reduction in cardiovascular events or microvascular complications compared to standard group patients who achieved A1c of 8.4%. However, the VADT Trial was underpowered for its main hypothesis tests (Duckworth, 2009). In the ADVANCE trial, intensive group patients had less progression to proteinuria (one less patient advancing to proteinuria for every 100 people in the intensive group over a five-year period of time), but no fewer eye complications in the intensive group than in the standard group. ACCORD analysis showed lower rates of early stage microvascular complications in the intensively treated group. Some patients, especially those



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with little comorbidity and long life expectancy, may benefit from more intensive glycemic goals as long as hypoglycemia does not become a barrier. However, the risk of lower glycemic targets may outweigh the potential benefits on microvascular complications for many patients (ACCORD, 2010b; Ismail-Beigi, 2010).

A meta-analysis analyzed five randomized controlled trials (UKPDS, PROactive, ADVANCE, VADT and ACCORD) for the effect of intensive glucose control on cardiovascular outcomes. Overall, this meta-analysis concluded that more intensive glucose control significantly reduced non-fatal myocardial infarct events and coronary heart disease events (non-fatal myocardial infarct and all-cardiac mortality) with no evidence of either a benefit or adverse effect on all-cause mortality. Heterogeneity among studies was noted with regard to all-cause mortality, suggesting that the impact of glycemic reduction on all-cause mortality may differ among different populations (Ray, 2009). A subset analysis from ACCORD, ADVANCE and VADT suggested that intensive glucose lowering has a modest (9%) but statistically significant reduction in major CVD outcomes, primarily non-fatal MI, with no significant effect on mortality. However, a pre-specified subgroup analysis suggested that major cardiovascular disease outcome reduction occurred in patients without known cardiovascular disease at baseline (Turnbull, 2009).

Glycosylated hemoglobin assays

Glycosylated hemoglobin assays provide an accurate indication of long-term glycemic control. Glycated hemoglobin is formed by the continuous non-enzymatic glycosylation of hemoglobin throughout the lifespan of an erythrocyte. The A1c assay yields an accurate measure of time-averaged blood glucose during the previous six to eight weeks. Clinically, it can assist in determining duration and severity of hyperglycemia and can help guide treatment.

Eating, physical activity or acute metabolic stress does not influence the A1c test. The test can be done at any time of day and does not require fasting.

Self-monitoring blood glucose (SMBG)

Self-monitoring blood glucose (SMBG) allows patients to evaluate his/her individual response to therapy and assess whether glucose targets are being achieved. Results of SMBG can be useful in preventing hypoglycemia and adjusting medications, medical nutrition therapy and physical activity (American Diabetes Association, 1994).

Major clinical trials assessing the impact of glycemic control on diabetes complications have included self-monitoring blood glucose testing (SMBG) as part of multifactorial interventions, suggesting that self-monitoring blood glucose is a component of effective therapy (American Diabetes Association, 2014). Several diabetes management strategies reliant on SMBG testing have demonstrated improved glucose control in patients (Polonsky, 2011; Weinger, 2011).

Table 1 gives ranges of self-monitored glucose readings that would be expected as goals for patients with the corresponding A1c level goals.




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Table 1. Ranges of self-monitored blood glucose values for various A1c goals

A1c Target Average Mean

Fasting Blood Glucose*

Average Mean Post- Prandial Blood

Glucose

Estimated Average Blood Glucose**

< 6% < 100 < 140 126 7% 90-130 < 180 154 8% 120-160 < 210 182 9% 160-190 < 240 211

* It is not recommended to achieve target fasting glucose values below 70 mg/dL. ** This average uses both fasting and post-prandial blood glucose readings from continuous

glucose monitors or from 7-point daily testing. Table 1 was developed by the diabetes work group based on data currently available from studies of frequently monitored glucose values and will be modified if necessary as further studies become available.

The frequency and timing of SMBG should be dictated by the particular needs and goals of the individual patient. Bedtime glucose goals vary dependent on the patient's treatment program, risks for hypoglycemia and time after last meal. Patients with T2DM on insulin typically need to perform self-monitoring blood glucose more frequently than those not using insulin, particularly if using glucose readings to guide mealtime insulin dosing. It is recommended that patients using multiple insulin injections perform SMBG prior to meals, snack or exercise or when low blood glucose is questioned (American Diabetes Association, 2014). The optimal frequency and timing of SMBG for patients with T2DM on oral or non-insulin injectable therapy are not known but should be sufficient to facilitate reaching glucose goals. SMBG should be performed more frequently when adding or modifying therapy; two-hour post-prandial glucose testing is useful in some patients. The role of SMBG in stable diet-treated patients with T2DM is not known.

Because the accuracy of SMBG is instrumental and user dependent, it is important for health care clinicians to evaluate each patient's monitoring technique and accuracy of equipment. In addition, optimal use of SMBG requires proper interpretation of the data. When appropriate, patients can be taught how to use the data to adjust food intake, exercise or pharmacological therapy to achieve specific glycemic goals.




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5. Education and Self-Management5.1 Nutrition Therapy


A qualified health professional (which may include a clinician, dietitian, nursing staff and pharmacist) should provide nutrition therapy to a patient diagnosed with T2DM as part of a global treatment plan.

Quality of Evidence: Moderate


Benefits: Nutrition therapy specifically activates patients by more intensively assessing eating and physical activity behaviors and nutrient intake, and provides counseling that results in improved health and may reduce complication of T2DM. Diabetes nutrition therapy can result in cost savings and improved outcomes such as reduction in A1c. Nutrition therapy can be personalized based upon the patients needs, comorbidities, existing chronic conditions and other key factors. Harms: Professionals who do not utilize evidence-based standards/protocols can promote expensive short-term strategies that limit food choices without scientific evidence that are not ultimately effective in improving long-term health. Patient activation can be difficult and may not be sustainable for the patient long term, and the increased cost for healthy foods may be a burden for some. Benefits-Harms Assessment: The benefit of having a patient activated and counseled based upon his/her needs and the increase of risk reduction outweighs the difficulty in achieving nutrition modification. Relevant Resources: Ajala, 2013; Estruch, 2013; Andrews, 2011; Azadbakhh, 2011; Elhayany, 2010; Brehm, 2009; Esposito, 2009; Robbins, 2008; Bruneroya, 2007; Nield, 2007; Ash, 2003

Recommendation Quality of Evidence and

Strength of Recommendation

A qualified health care professional (which may include a clinician, nursing staff, pharmacist, and registered dietitian) should counsel a patient diagnosed with T2DM to modify his/her diet to reduce sodium intake to < 2,300 mg/day (Strong). Clinicians may counsel patients diagnosed with T2DM and hypertension to further reduce their sodium intake (Weak).

Quality of Evidence: High

Strength of Recommendation: Strong/Weak

Benefits: Incrementally lower sodium intakes have shown beneficial effects on blood pressure and mitigation of cardiovascular risk factors with such meal plans as the DASH diet. Harms: There is difficulty in achieving both low-sodium recommendations and a nutritionally adequate diet, given such concerns as cost, palatability and availability of lower sodium food products. Benefits-Harms Assessment: The beneficial effects on blood pressure and mitigation of cardiovascular risk factors outweigh the inconvenience and cost of finding a diet with a reduced sodium intake. Sodium intake < 1,500 mg/day has shown to be associated with a small increase in mortality, and counseling a patient to reduce sodium intake to < 2,300 mg/day should be considered only on an individual basis with consideration. Relevant Resources: He, 2013; Suckling, 2010




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A qualified health care professional (which may include a clinician, dietitian, nursing staff and pharmacist) may give a patient diagnosed with T2DM a meal plan that incorporates monitoring carbohydrates.

Quality of Evidence: Moderate


Benefits: A customized diabetes meal plan that includes the amount of carbohydrate in meals and snacks to improve postprandial glycemia is effective in achieving glycemic control. Carbohydrate intake has a direct effect on postprandial glucose levels and is the macronutrient most of concern in glycemic management. Simplified plate methods that including portion-controlled carbohydrate food sources may be better suited for patients with numeracy and literacy concerns. Carbohydrate intake from vegetables, fruits, whole grains, legumes and dairy products should be advised over intake from other carbohydrate sources, especially those that contain added fats, sugars or sodium. Harms: Meal plans that do not adjust for total amount of carbohydrates can result in higher than desired target ranges for postprandial blood glucoses and HgbA1c. If the patient is not given a meal plan at the appropriate literacy level, the ability for the patient to effectively monitor carbohydrates may be difficult and produce less than ideal outcomes. Benefits-Harms Assessment: Monitoring carbohydrate intake, whether by carbohydrate counting or experience-based estimation, remains a key strategy in achieving glycemic control and outweighs the difficulty in achieving nutrition modification. Relevant Resources: Ajala, 2013; Estruch, 2013; Azadbakht, 2011; Wiebe, 2011; Elhayany, 2010; Brehm, 2009; Esposito, 2009; Thomas, 2009b; Brunerova, 2007

Supplemental InformationNutrition assessment

Clinicians providing nutrition therapy should complete a nutrition assessment, and provide tailored educa-tion and counseling based on the individual needs of the person with diabetes. While many standardized meal plans and menus are available in print or Web-based, it is through the collaborative development of individualized nutrition interventions with ongoing support for behavior change that best facilitates achievement of patients' health goals (Everett, 2013). Nutrition education should be delivered by health professionals with appropriate training, knowledge and skills, and of sufficient duration and quality to meet patients' needs effectively (Miller, 2001).

Goals and eating patterns

Goals of nutrition therapy for diabetes promote healthful eating patterns designed to lower glucose, blood pressure, and alter lipid profiles to lower cardiovascular risk factors, emphasizing a variety of nutrient-dense foods in appropriate portion sizes to improve overall health (Everett, 2013). Eating patterns or dietary patterns are combinations of different foods or food groups that characterize relationships between nutrition and healthy promotion or disease prevention. Eating patterns include Mediterranean-style, DASH, vegetarian or vegan, low carbohydrate and low fat. Eating plans should take into account individual personal and cultural preferences, health literacy and numeracy, willingness to change behaviors and metabolic goals. Major metabolic goals are to attain individualized glycemic, blood pressure and lipid goals, and achieve and maintain body weight goals to delay and prevent complications of diabetes (Everett, 2013).

Macronutrients

A recent systematic review provides evidence that modifying the amount of macronutrients can improve glycemic control, weight and lipids in people with diabetes. Low-carbohydrate, low-glycemic index (GI), Mediterranean and high-protein diets reduced hemoglobin A1c by 0.12-0.5% compared to comparison or control diets. These hemoglobin A1c reductions were significant, with a reduction of 0.5% that was similar to that achieved by using medication and associated with lower risk of microvascular complications (Ajala, 2013). However, while other various meta-analysis and systematic reviews have been conducted, there is no conclusive evidence regarding an ideal macronutrient distribution for all people with diabetes (Everett, 2013). Another recent systematic review found there is no ideal mix of macronutrients that can be applied and that macronutrient proportions should be individualized (Wheeler, 2012).




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Meal planning approaches

There are multiple meal planning approaches that can be used as effective nutrition interventions. Examples include carbohydrate counting, simplified healthful food choices (i.e., the Plate Method), and individualized meal plans based on percentages of macronutrients, exchange lists or glycemic index. For individuals using fixed daily insulin doses, consistent carbohydrate intake with respect to time and amount can reduce risk of hypoglycemia and improve glycemic control (Everett, 2013).

Carbohydrate intake

There is insufficient evidence to recommend a specific amount of carbohydrate intake for all people with diabetes. Despite the conflicting evidence evaluating the effect of differing percentages of carbohydrates, monitoring carbohydrates remains a useful strategy. The quantity and the type of carbohydrate in a food influence blood glucose level, and the total amount of carbohydrate is the primary predictor of glycemic response. Therefore, the effect of the amount of carbohydrates and available insulin on postprandial blood glucose should be considered in developing a meal plan. Monitoring carbohydrate intake, either by carbo-hydrate counting or experience-based estimation, remains a key strategy in achieving glycemic control (Everett, 2013).

Sucrose

It has been demonstrated that the substitution of sucrose for starch for up to 35% of calories may not affect glycemia or lipid levels. Since foods high in sucrose are high in calories, substitution should be made to ensure nutrient density of overall eating pattern. There is evidence from studies of individuals without diabetes that because of rapidly absorbable carbohydrates (such as sucrose or high-fructose corn syrup) large quantities of sugar-sweetened beverages (SSBs) should be avoided to lower risk of weight gain and worsening of cardiometabolic risk factors (Everett, 2013).

Fiber

People with diabetes should consume at least the amount of fiber and whole grain recommended for the general population. Encourage consuming a wide variety of fiber-containing foods such as legumes, fiber-rich cereals, fruits, vegetables and whole grain products to achieve fiber intake goals of 14 g/1,000 calories or about 25 g/day for adult women and 38 g/day for adult men, and meet recommendations to consume at least half of all grains as whole grains (Everett, 2013).

Glycemic index

A recent systematic review on low-glycemic index diets concluded a low-GI diet can decrease HgbA1c by 0.5%, which was statistically significant (Thomas, 2009)

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